protective effects of saxagliptin (and vitamin d3) on β cell function in adult-onset latent autoimmune diabetes

Conditions: Diabetes Mellitus, Type 1

Summary: the main purpose of this study is to evaluate whether saxagliptin or (and vitamin d3) with metformin (and insulin) therapy can better protect islet β cell function than metformin(and insulin) .

lada is actually a form of type 1 diabetes, which is caused by autoimmune damage of islet β cells and triggered by environmental factors based on genetic susceptibility. lada shows some characteristics of type 2 diabetes at its onset, which develops slowly and latent, and easily be misdiagnosed as type 2 diabetes due to slowly β cell function deterioration. this is a multi-center, open- label, 1:1:1 randomized controlled trial to investigate the protective effects of saxagliptin and vitamin d3 in lada patients. the study comprises the 0-6weeks of screening period and the 104-week intervention period. after obtaining the informed consent，the screening will find out the eligible patients according to the inclusion/exclusion criteria, then the patients will be randomized to the 104-week intervention period. subjects will be randomized into one of the three groups(arms) through central dynamic randomization: metformin (and insulin), metformin(and insulin) +saxagliptin, metformin(and insulin) +saxagliptin+vitamin d3. our previous randomized- controlled pilot study showed that dipeptidyl peptidase 4 (dpp-4) inhibitors could significantly improve islet β-cell function in patients with lada. the main purpose of this study: to evaluate whether saxagliptin (and vitamin d3) with metformin (and insulin) therapy can better protect islet β cell function than metformin (and insulin).

Eligibility criteria:
inclusion criteria: 1. volunteer to participate in the study with informed consent; 2. the lada patients to be included in this study are defined as: (1) meet the 1999 who diagnostic criteria for diabetes mellitus; (2) age at diagnosis of dm ≧ 18 years old; (3) glutamic acid decarboxylase antibody (gada) positive; (4) serum fasting c-peptide ≥ 100 pmol/l or 2-hour postprandial c-peptide≥ 200 pmol/l; 3. age between 18-70 years old; 4. diabetes duration \<4 year; 5. outpatient or inpatient. exclusion criteria: 1. pregnancy, breastfeeding or planned pregnancy within two years; 2. gestational diabetes mellitus or other specific types of diabetes; 3. allergic to saxagliptin, vitamin d3 and their excipient; 4. treatment with any anti-diabetic medication other than insulin in the last 8 weeks prior to randomization; 5. use of systemic corticosteroids therapy (oral, intravenous) continuously for more than 7 days over the past 6 months; 6. treatment with cytochrome p450 3a4/5 (cyp450 3a4/5) inhibitor; 7. alanine aminotransferase (alt) or aspartate transaminase(ast) more than 3 times of the normal upper limit, total bilirubin (tbil) more than 2 times of the normal upper limit; 8. creatinine levels ≧ 1.5 mg/dl(132μmol/l) for males and ≧ 1.4 mg/dl (123μmol/l) for females or creatinine clearance ≦ 50 ml/min; 9. history of malignant tumors; 10. history of mental disorders; 11. history of alcohol abuse or illegal drug abuse; 12. serious systemic disease which the investigators think would not be suitable for the study.

Keywords: lada saxagliptin vitamin d3 c-peptide